Generally, legacy fluorometry systems employ either “right angle” or “front face” optics. Right angle optics is where the detector is placed at right angles to the excitation source. This serves to minimize interference from the excitation source. However, these systems are subject to “inner filtering” problems where the light fluoresced by the sample is filtered out by the sample under test. Front facing optics is where the detector is placed at an angle between either 30-40 degrees or 50-60 degrees to the excitation source. Front facing optics overcomes inner filtering but is unable to relate fluorescent intensity to analyte concentration over a very broad range for analytes having a high extinction coefficient. These problems have limited the application of fluorometry techniques in the area of noninvasive analysis, particularly blood and tissue analysis.
Significant advances in modern technology have failed so far to provide any relief for such problems.
Many of these technologies are disclosed in a broad spectrum of patents and patent applications, including:
U.S. Pat. No. 6,252,657 to Bohnenkamp discloses a reflection fluorometer using light guides to test samples placed in a capillary tube. However this approach is not suitable for non-invasive measurement.
U.S. Pat. No. 5,785,658 to Benaron discloses a tool for nondestructive interrogation of the tissue including a light source emitter and detector which may be mounted directly on a surgical tool in a tissue contacting surface for interrogation or mounted remotely and guided to the surgical field with fiber optic cables. This device is also invasive.
U.S. Pat. No. 5,933,232 to Atzler discloses a measurement station for microtitration plates. The system applies fluorometry to solutions in curvettes, which are not compatible with non-invasive use.
U.S. Pat. No. 6,013,034 to Da Cunha Vaz discloses an Ocular Fluorometer for use in taking non-invasive reflective fluorometric readings of the human eye.
U.S. Pat. No. 4,178,917 to Shapiro discloses a method and system for the non-invasive detection of zinc protoporphyrin (ZPP) in erythrocytes wherein a light source is applied to the skin of the patient. However, the approach uses front facing optics so it is subject to the inherent limitations of front facing optics discussed above.
In summary, the prior art provides a broad range of alternatives to invasive fluorescent spectroscopy. The prior art also provides some solutions to non-invasive spectroscopy using either front facing or reflective optics. However these non-invasive solutions are subject to problems of inner filtering and/or inability to correlate fluorescent intensity to analyte concentration. As a result, existing solutions are inapplicable to a whole host of new applications (such as blood analyte measurement) which demand non-invasive testing, accuracy, broad diagnostic capability and convenient usage.